title: Periconception maternal characteristics and embryonic growth trajectories: the Rotterdam Predict study.
abstract: OBJECTIVE
  Are maternal characteristics and lifestyle factors associated with human embryonic growth trajectories?
  
  
  CONCLUSIONS
  Periconception maternal age is associated with increased, and smoking and alcohol use with decreased embryonic growth trajectories, estimated with crown-rump length (CRL) measurements.
  
  
  BACKGROUND
  Fetal weight is associated with health and disease in later life. Maternal characteristics and lifestyle factors affect fetal growth in the second and third trimesters of pregnancy and at birth; however, little is known about the association of these characteristics with first trimester embryonic growth.
  
  
  METHODS
  In a tertiary centre, pregnant women were recruited and enrolled in a prospective periconception cohort study before 8 weeks of gestation. We selected 87 spontaneously conceived singleton pregnancies of women recruited in 2009 and 2010 that ended in non-malformed live births.
  
  
  METHODS
  We performed weekly three-dimensional ultrasound scans from enrolment up to 13 weeks of gestation. At enrolment, a questionnaire was completed. Embryonic CRL measurements were performed using the V-Scope software in the BARCO I-Space. Associations between maternal characteristics and embryonic growth were assessed using square root transformed CRL as response in linear mixed model analyses, adjusted for potential confounders.
  
  
  RESULTS
  Four hundred and ninety-six scans from 87 pregnancies were included. In the multivariable analysis, maternal age was positively associated with first trimester CRL (difference per maternal year of age 0.024√mm (95% confidence interval (CI) 0.009, 0.040), P = 0.001). At 6 and 12 weeks of gestation, the CRL of an embryo from a 40-year-old mother was estimated 2.0 mm (61%) and 7.2 mm (14%) larger, respectively, compared with an embryo from a 20-year-old mother. Smoking of 10 or more cigarettes per day was negatively associated with CRL (difference -0.211√mm (95% CI -0.416, -0.006), P = 0.04), with embryos that were 0.9 mm (18.7%) and 3.1 mm (5.5%) smaller at 6 and 12 weeks, respectively, compared with non-smokers. Periconception alcohol use was negatively associated with CRL growth rate (difference -0.0025√mm (95% CI -0.0047, -0.0003)/day gestational age, P = 0.022), with embryos that were 0.2 mm (3%) and 1.1 mm (2%) smaller at 6 and 12 weeks, respectively, compared with non-alcohol users. Parity, BMI and moment of initiation of folic acid use were not significantly associated with embryonic CRL.
  
  
  CONCLUSIONS
  Due to the selection of pregnancies in a tertiary centre and the small number of pregnancies, the external validity of the results has to be confirmed using larger sample sizes and other population-based periconception cohort studies.
  
  
  CONCLUSIONS
  The association of maternal age and smoking with embryonic growth is in line with previous literature, whereas the association between embryonic growth and alcohol use is a new finding. However, concerning exposure to alcohol, the effect estimate was small and it is questionable whether this is of clinical value. More research is warranted to unravel underlying mechanisms and to assess the implications for preconception and early pregnancy care, such as the development and implementation of effective lifestyle interventions.
  
  
  BACKGROUND
  The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, 3015 GD Rotterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: van Uitert
authors.forename: N
authors.initials: N
authors.lastname: van der Elst-Otte
authors.forename: J J
authors.initials: JJ
authors.lastname: Wilbers
authors.forename: N
authors.initials: N
authors.lastname: Exalto
authors.forename: S P
authors.initials: SP
authors.lastname: Willemsen
authors.forename: P H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: A H J
authors.initials: AH
authors.lastname: Koning
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D018568:Crown-Rump Length; D005260:Female; D047109:Fetal Development; D020567:Fetal Weight; D006801:Humans; D008137:Longitudinal Studies; D008423:Maternal Age; D009426:Netherlands; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects; D016216:Ultrasonography, Prenatal
keywords: crown-rump length; embryonic development; first trimester; pregnancy; three-dimensional imaging